Diabetes mellitus is a metabolic disorder characterized by chronically elevated levels of blood glucose, or hyperglycemia, which results from a reduction or absence of activity of the peptide hormone insulin. Insulin, which is produced and secreted by the beta cells of the pancreas, promotes the utilization of glucose and is essential to the maintenance of blood levels of glucose within the normal physiological range.
Included within the scope of the term diabetes mellitus are two states: Type 1, also known as insulin-dependent diabetes mellitus (IDDM), and Type 2, or non-insulin-dependent diabetes mellitus (NIDDM). Type 1 diabetes is characterized by a deficiency or absence of insulin, such that the level of blood glucose cannot be maintained within the normal range, and must be treated by administration of insulin to the patient. Type 2 diabetes is characterized by either or both a state of insulin resistance or impaired insulin sensitivity or reduced insulin secretion, that is, a state in which insulin does not produce the expected decrease in blood glucose concentrations, resulting in hyperglycemia.
Insulin and insulin analogs are commonly administered to diabetic patients, particularly Type 1 patients, in an injectable composition which comprises a pharmaceutically acceptable carrier and typically one or more conventional excipients. It is believed to be desirable to include in such compositions one or more peptides, in particular peptides that are naturally secreted by the pancreas together with insulin in non-diabetics. Such peptides are herein referred to as “insulin-related peptides”.
One problem that is expected to arise in preparing such compositions is that most peptides are not as stable thermally as insulin. A need therefore exists for a thermally stable composition that includes insulin or an insulin analog together with at least one insulin-related peptide, peptide fragment or peptide analog.
Certain therapies for Type 2 diabetes do not require the administration of insulin. Such therapies, however, typically act by stimulating the release of insulin from the pancreatic beta cells. In these therapies, the pancreas can be subjected to undesirable stress. A need therefore also exists for an improved composition that does not cause excessive stress to the pancreas of the patient to whom the composition is administered.
A need also exists for method of preparing such compositions and administering such compositions to a patient.